The vertebrate immune system includes numerous interacting proteins involved in the recognition and elimination of parasitic organisms. The general goal of this research is to understand the evolution of key molecular components of this system, particularly the molecules encoded by the major histocompatibility complex (MHC), and to understand how immunogenic proteins of parasitic organisms have evolved under natural selection exerted by the host's immune system. The MHC is a multi-gene family encoding cell-surface glycoproteins which play an important role in the immune system, binding foreign peptides and presenting them to T cells, thereby triggering an appropriate immune response. Certain MHC loci are highly polymorphic in humans and other vertebrates, and recent analyses of DNA sequence data have provided evidence that this polymorphism is maintained by positive selection favoring the ability to bind and present a variety of foreign peptides. Therefore the MHC provides an excellent system for studying the evolution of immune recognition and the role of infectious disease as an agent of natural selection. The methods will involve statistical analysis of published DNA sequences, of which there are a large number now available for MHC genes of several mammalian species; for other immune system genes; and for genes of parasites encoding immunogenic proteins. The purpose of these analyses will be as follows: (1) to test the hypothesis that polymorphism at MHC loci is maintained by overdominant selection relating to disease resistance and to understand the role of recombination in generating new MHC alleles; (2) to test the hypothesis that the vertebrate immune system has exerted selection on proteins of parasitic organisms to evade recognition by the host; and (3) to understand the evolutionary history and patterns of co-evolution of MHC genes and other genes playing important roles in the immune system (including T cell receptors, integrins, Fc receptors, the C3/C4/C5 complement component family, and the ABC family of transmembrane transporters).